Erythema multiforme is an acute syndrome often following an infection. Our preliminary clinical pathogenetic study has demonstrated a high association of erythemia multiforme with preceding herpes simplex virus infection. Our hypothesis regarding the pathogenesis of herpes simplex-associated erythema multiforme is that it involves immune complex formation. We believe that herpes-associated erythema multiforme may pose a model of in situ immune complex formation. If herpes glycoprotein antigens are released into the circulation of these patients, it would seem reasonable that they would tend to bind to the surface of epidermal cells. Since herpes viruses are epidermotrophic these proteins are involved in the binding of the virus to the membrane of epidermal cells. Subsequent combinations of antibody with membrane-bound antigen might lead to destruction of cells in the epidermis as seen in erythema multiforme. We plan to utilize enzyme immunoassays and immunofluorescent techniques to evaluate HSV antigens and antibodies in circulating immune complexes and skin biopsies obtained from erythema multiforme patients.